Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.
Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.
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DOI：
10.1158/1078-0432.ccr-14-0990
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发表时间：
2015-01-15
期刊：
影响因子：
--
通讯作者：
Jackson A
中科院分区：
文献类型：
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作者：
O'Connor JP;Rose CJ;Waterton JC;Carano RA;Parker GJ;Jackson A
肿瘤表现出基因组和表型的异质性，这对预后有重要意义，并可能影响治疗反应。成像可以通过量化密度或MRI信号松弛速率等基本生物物理参数，通过测量血流、缺氧、代谢、细胞死亡等表型特征，通过绘制生化途径和细胞信号网络的空间分布图，来量化单个肿瘤的结构和功能的空间差异。这些方法可以确定一种肿瘤比另一种肿瘤更具异质性或更少异质性，并可以识别具有不同生物学特性的子区域。在这篇文章中，我们回顾了目前用于量化肿瘤内空间异质性的图像分析方法。我们讨论了如何分析肿瘤内的异质性可以提供比更简单的生物标记物，如肿瘤大小和平均功能更有利的。我们考虑如何将成像方法与基因组和病理数据相结合，而不是孤立地发展。最后，我们确定了在常规使用肿瘤内异质性测量来指导患者护理之前必须克服的挑战。
Tumors exhibit genomic and phenotypic heterogeneity which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks. These methods can establish whether one tumor is more or less heterogeneous than another and can identify sub-regions with differing biology. In this article we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, rather than be developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care.